The means by which the body defends itself against pathogenic agents such as bacteria, viruses and tumor cells involve incompletely understood interactions between the humoral and the cellular arms of the immune system. Although multiple antibody-dependent defense mechanisms have been identified, less is known about inherent antibody-independent pathways which may be important in host defense, particularly early when specific antibody may not yet be present. This proposal addresses the possibility that the first component (C1) of the human complement (C) system, which is a potent mediator of numerous biological reactions, functions in this manner. Support for this hypothesis comes from the observation that certain bacteria, viruses and tumor cells bind and activate C1 without the participation of antibody. Activation is followed by dissociation of C1 with exposure of previously masked portions of one of the constituents of C1, C1q. We have previously shown that there is a specific cell surface receptor for this part of C1q on certain leukocyte populations, namely polymorphonuclear cells, monocytes, B cells and a subpopulation of non-B, non-T lymphocytes. Thus there exists a mechanism to bring certain bacteria, viruses and tumor cells to the surface of those cells through a C1q bridge. This proposal focuses on the physiological consequences of the interaction with polymorphonuclear cells, monocytes and null cells of C1q bound to such nonimmune activators. The rate of binding, ingestion and destruction of such bacteria, virus and tumor cells by the phagocytic cells will be determined. In addition, extracellular killing, and the mechanism thereof, will be examined. Also to be appraised is the expression of the C1q receptor and associated biological function during the differentiation of human monocytes into macrophages and finally activated macrophages. Finally, the possibility that C1q synthesized by macrophages functions as a cellular Fc receptor will be explored. It is hoped that these studies will provide insight into the biological importance of a previously unappreciated complement-dependent, nonimmume or inherent defense mechanism.